Prenatal diagnosis of combined methylmalonic acidemia and homocystinuria cobalamin C type using clinical exome sequencing and targeted gene analysis

Abstract Background Combined methylmalonic acidemia and homocystinuria is a rare inherited disorder of intracellular cobalamin metabolism caused by biallelic variants in one of the following genes: MMACHC (cblC), MMADHC (cblD), LMBRD1 (cblF), ABCD4 (cblJ), THAP11 (cblX‐like), and ZNF143 (cblX‐like),...

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Autores principales:	Narae Hwang, Ja‐Hyun Jang, Eun‐Hae Cho, Rihwa Choi, Suk‐Joo Choi, Hyung‐Doo Park
Formato:	article
Lenguaje:	EN
Publicado:	Wiley 2021
Materias:	combined methylmalonic acidemia with homocystinuria prenatal diagnosis whole exome sequencing Genetics QH426-470
Acceso en línea:	https://doaj.org/article/b07b422cf45743238f53c5b6c376b936
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spelling	oai:doaj.org-article:b07b422cf45743238f53c5b6c376b9362021-11-21T19:38:53ZPrenatal diagnosis of combined methylmalonic acidemia and homocystinuria cobalamin C type using clinical exome sequencing and targeted gene analysis2324-926910.1002/mgg3.1838https://doaj.org/article/b07b422cf45743238f53c5b6c376b9362021-11-01T00:00:00Zhttps://doi.org/10.1002/mgg3.1838https://doaj.org/toc/2324-9269Abstract Background Combined methylmalonic acidemia and homocystinuria is a rare inherited disorder of intracellular cobalamin metabolism caused by biallelic variants in one of the following genes: MMACHC (cblC), MMADHC (cblD), LMBRD1 (cblF), ABCD4 (cblJ), THAP11 (cblX‐like), and ZNF143 (cblX‐like), or a hemizygous variant in HCFC1 (cblX). Prenatal diagnosis of combined methylmalonic acidemia with homocystinuria is crucial for high‐risk couples since the disorder can be life‐threatening for offspring. We would like to describe two infant deaths both of which are likely attributable to cblC despite not having a genetic confirmation, and subsequent pregnancy and prenatal genetic testing. Methods Parental clinical exome sequencing and targeted Sanger sequencing of MMACHC gene in amniotic fluid was performed to check the carrier status of the fetus. Results Parental clinical exome sequencing revealed a heterozygous pathogenic variant [NM_015506.2:c.217C>T (p.Arg73)] in the MMACHC gene of the mother and [NM_015506.2:c.609G>A (p.Trp203)] in the MMACHC gene of the father. Targeted Sanger sequencing of MMACHC gene in amniotic fluid revealed that the fetus carried only one nonsense variant [NM_015506.2:c.609G>A (p.Trp203*)], which was inherited from the father. The mother delivered a healthy baby and the neonate did not show any symptoms or signs of combined methylmalonic acidemia and homocystinuria after birth. Conclusion We present a case of prenatal diagnosis with parental exome sequencing, which successfully diagnosed the carrier status of the fetus and parents in a combined methylmalonic acidemia and homocystinuria family.Narae HwangJa‐Hyun JangEun‐Hae ChoRihwa ChoiSuk‐Joo ChoiHyung‐Doo ParkWileyarticlecombined methylmalonic acidemia with homocystinuriaprenatal diagnosiswhole exome sequencingGeneticsQH426-470ENMolecular Genetics & Genomic Medicine, Vol 9, Iss 11, Pp n/a-n/a (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	combined methylmalonic acidemia with homocystinuria prenatal diagnosis whole exome sequencing Genetics QH426-470
spellingShingle	combined methylmalonic acidemia with homocystinuria prenatal diagnosis whole exome sequencing Genetics QH426-470 Narae Hwang Ja‐Hyun Jang Eun‐Hae Cho Rihwa Choi Suk‐Joo Choi Hyung‐Doo Park Prenatal diagnosis of combined methylmalonic acidemia and homocystinuria cobalamin C type using clinical exome sequencing and targeted gene analysis
description	Abstract Background Combined methylmalonic acidemia and homocystinuria is a rare inherited disorder of intracellular cobalamin metabolism caused by biallelic variants in one of the following genes: MMACHC (cblC), MMADHC (cblD), LMBRD1 (cblF), ABCD4 (cblJ), THAP11 (cblX‐like), and ZNF143 (cblX‐like), or a hemizygous variant in HCFC1 (cblX). Prenatal diagnosis of combined methylmalonic acidemia with homocystinuria is crucial for high‐risk couples since the disorder can be life‐threatening for offspring. We would like to describe two infant deaths both of which are likely attributable to cblC despite not having a genetic confirmation, and subsequent pregnancy and prenatal genetic testing. Methods Parental clinical exome sequencing and targeted Sanger sequencing of MMACHC gene in amniotic fluid was performed to check the carrier status of the fetus. Results Parental clinical exome sequencing revealed a heterozygous pathogenic variant [NM_015506.2:c.217C>T (p.Arg73)] in the MMACHC gene of the mother and [NM_015506.2:c.609G>A (p.Trp203)] in the MMACHC gene of the father. Targeted Sanger sequencing of MMACHC gene in amniotic fluid revealed that the fetus carried only one nonsense variant [NM_015506.2:c.609G>A (p.Trp203*)], which was inherited from the father. The mother delivered a healthy baby and the neonate did not show any symptoms or signs of combined methylmalonic acidemia and homocystinuria after birth. Conclusion We present a case of prenatal diagnosis with parental exome sequencing, which successfully diagnosed the carrier status of the fetus and parents in a combined methylmalonic acidemia and homocystinuria family.
format	article
author	Narae Hwang Ja‐Hyun Jang Eun‐Hae Cho Rihwa Choi Suk‐Joo Choi Hyung‐Doo Park
author_facet	Narae Hwang Ja‐Hyun Jang Eun‐Hae Cho Rihwa Choi Suk‐Joo Choi Hyung‐Doo Park
author_sort	Narae Hwang
title	Prenatal diagnosis of combined methylmalonic acidemia and homocystinuria cobalamin C type using clinical exome sequencing and targeted gene analysis
title_short	Prenatal diagnosis of combined methylmalonic acidemia and homocystinuria cobalamin C type using clinical exome sequencing and targeted gene analysis
title_full	Prenatal diagnosis of combined methylmalonic acidemia and homocystinuria cobalamin C type using clinical exome sequencing and targeted gene analysis
title_fullStr	Prenatal diagnosis of combined methylmalonic acidemia and homocystinuria cobalamin C type using clinical exome sequencing and targeted gene analysis
title_full_unstemmed	Prenatal diagnosis of combined methylmalonic acidemia and homocystinuria cobalamin C type using clinical exome sequencing and targeted gene analysis
title_sort	prenatal diagnosis of combined methylmalonic acidemia and homocystinuria cobalamin c type using clinical exome sequencing and targeted gene analysis
publisher	Wiley
publishDate	2021
url	https://doaj.org/article/b07b422cf45743238f53c5b6c376b936
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Prenatal diagnosis of combined methylmalonic acidemia and homocystinuria cobalamin C type using clinical exome sequencing and targeted gene analysis

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